Decoding microglia responses to psychosocial stress reveals blood-brain barrier breakdown that may drive stress susceptibility
Michael L. Lehmann*1, Thaddeus K. Weigel1, Hannah A. Cooper1, Abdel G. Elkahloun2, Stacey L. Kigar1, and Miles Herkenham1 1Section on Functional Neuroanatomy, Intramural Research Program, National Institute of Mental Health, NIH, Bethesda, MD 20892 USA; 2Division of Intramural Research Programs Microarray Core Facility, National Institutes of Health, Bethesda, MD, 20892 USA *Corresponding author at: Bldg. 35, Rm. 1C911, Bethesda, MD 20892-3724 e-mail address: email@example.com
An animal's ability to cope with or succumb to deleterious effects of chronic psychological stress may be rooted in the brain's immune responses manifested in microglial activity. Mice subjected to chronic social defeat (CSD) were categorized as susceptible (CSD-S) or resilient (CSD-R) based on behavioral phenotyping, and their microglia were isolated and analyzed by microarray. Microglia transcriptomes from CSD-S mice were enriched for pathways associated with CNS healing to sterile injury, including inflammation, oxidative stress, debris clearance, and wound resolution. Histochemical experiments confirmed the array predictions: CSD-S microglia showed elevated phagocytosis and oxidative stress, and the brains of CSD-S but not CSD-R or HC mice showed vascular leakage of intravenously injected fluorescent tracers. The results suggest that the inflammatory profile of CSD-S microglia may be precipitated by leakage of blood-borne substances into brain parenchyma. We hypothesize that these CNS-centric responses contribute to the stress-susceptible behavioral phenotype.
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